Enter a Search String

Special character and space not allowed in the query term. Search string should be at least 2 characters long.

Search in:

ALL Accession Pathway Molecule Enzyme Reaction Connected to

Search for

Match

Anything Exact Word Starting With

By

Name Notes Model

Molecule Parameter List for I1

The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network. The text color of a molecule is highlighted by color.

Statistics

I1 participated as	Molecule	Sum total of	Enzyme	Substrate of an enzyme	Product of an enzyme	Substrate in Reaction	Product in Reaction
No. of occurrences	2	0	0	2	6	0	2

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
CaMKII_noPKA_ model3	62	Network	Shared_Object_CaMKII_noPKA_model3,  CaMKII,  CaM,   PP1,  PP2B,  PP1_PSD
This is the model of CaMKII bistability, model 3. It exhibits bistability in CaMKII activation due to autophosphorylation at the PSD and local saturation of PP1. This version of model 3 does not include the full PKA regulatory pathway, and instead has a predefined initial amount of active PKA.

I1 acting as a Molecule in  CaMKII_noPKA_model3 Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
I1	CaMKII_noPKA_ model3 Accession No. : 62	PP1 Pathway No. : 260	1.8	0.09	No
I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM.
I1	CaMKII_noPKA_ model3 Accession No. : 62	PP1_PSD Pathway No. : 262	4	0.01	No
I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM.

I1 acting as a Substrate for an Enzyme in  CaMKII_noPKA_model3 Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PKA-active  / PKA-phosph-I1	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	7.50008	9	4	explicit E-S complex	Substrate I1 Product I1*
	#s from Bramson et al CRC crit rev Biochem 15:2 93-124. They have a huge list of peptide substrates and I have chosen high-ish rates. These consts give too much PKA activity, so lower Vmax 1/3. Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast). Also lower Km 1/3 so k1 = 1e-5 Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on phosphokinase beta.
2	PKA-active  / PKA-phosph-I1_ PSD	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	7.50008	9	4	explicit E-S complex	Substrate I1 Product I1*

I1 acting as a Product of an Enzyme in  CaMKII_noPKA_model3 Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PP2A  / PP2A-dephosph-I1	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	15.9999	2	4.1667	explicit E-S complex	Substrate I1* Product I1
	PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6
2	PP2A  / PP2A-dephosph-I1 _ PSD	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	15.9999	2	4.1667	explicit E-S complex	Substrate I1* Product I1
	PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6
3	CaNAB-Ca4  / dephosph_ inhib1_noCaM	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	4.97079	0.034	4	explicit E-S complex	Substrate I1* Product I1
	The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034
4	CaNAB-Ca4  / dephosph_ inhib1_noCaM_ PSD	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	4.97071	0.034	4	explicit E-S complex	Substrate I1* Product I1
	The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034
5	CaM_Ca_n-CaNAB  / dephosph_inhib1	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	4.97079	0.34	4	explicit E-S complex	Substrate I1* Product I1
6	CaM_Ca_n-CaNAB  / dephosph_ inhib1_PSD	CaMKII_noPKA_ model3 Accession No. : 62	Shared_Object_ CaMKII_noPKA_ model3 Pathway No. : 257	4.97071	0.34	4	explicit E-S complex	Substrate I1* Product I1

I1 acting as a Product in a reaction in  CaMKII_noPKA_model3 Network

Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reaction are not consider.

	Name	Accession Name	Pathway Name	Kf	Kb	Kd	tau	Reagents
1	dissoc-PP1-I1	CaMKII_noPKA_ model3 Accession No. : 62	PP1 Pathway No. : 260	1 (s^-1)	0 (uM^-1 s^-1)	-	-	Substrate PP1-I1 Product I1 PP1-active
	Let us assume that the equil in this case is very far over to the right. This is probably safe.
2	dissoc-PP1-I1	CaMKII_noPKA_ model3 Accession No. : 62	PP1_PSD Pathway No. : 262	1 (s^-1)	0 (uM^-1 s^-1)	-	-	Substrate PP1-I1 Product I1 PP1-active_PSD
	Let us assume that the equil in this case is very far over to the right. This is probably safe.